Wednesday, September 14, 2016

Infanrix-IPV+Hib





1. Name Of The Medicinal Product



INFANRIX-IPV+Hib powder and suspension for suspension for injection



Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus type b conjugate vaccine (adsorbed)


2. Qualitative And Quantitative Composition



A 0.5 ml dose of vaccine contains

































Diphtheria toxoid1

not less than 30 International Units (IU)


Tetanus toxoid1



not less than 40 International Units (IU)

Bordetella pertussis antigens
 

Pertussis toxoid1

25 µg

Filamentous haemagglutinin1

25 µg

Pertactin1

8 µg


Poliovirus (inactivated)


 

type 1 (Mahoney strain)2

40 D-antigen unit

type 2 (MEF-1 strain)2

8 D-antigen unit

type 3 (Saukett strain)2

32 D-antigen unit

Haemophilus type b polysaccharide
 

(polyribosylribitol phosphate)

10 µg

conjugated to tetanus toxoid as carrier protein

approximately 30 µg

1Adsorbed on aluminium hydroxide, hydrated

0.5 milligrams Al

2Propagated in VERO cells
 


For a full list of excipients, see section 6.1.



3. Pharmaceutical Form



Powder and suspension for suspension for injection.



The diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis (DTPa-IPV) component is a turbid white suspension.



The lyophilised Haemophilus influenzae type b (Hib) component is a white powder.



4. Clinical Particulars



4.1 Therapeutic Indications



INFANRIX-IPV+Hib is indicated for active immunisation against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b disease from the age of 2 months.



INFANRIX-IPV+Hib is not suitable for use in children over 36 months of age.



4.2 Posology And Method Of Administration



Posology



Primary vaccination:



The primary vaccination schedule consists of two or three doses given in accordance with official recommendations. The minimum age at the time of the first dose is 2 months. Subsequent doses of the primary course should be separated by a minimum interval of four weeks.



Booster vaccination:



After primary vaccination with two doses, a booster dose of INFANRIX-IPV+Hib must be given at least 6 months after the last priming dose, preferably between 11 and 13 months of age.



After primary vaccination with three doses, a booster dose of Hib conjugate vaccine (monovalent or combined) must be administered. The timing of this Hib conjugate vaccine booster dose should be in accordance with official recommendations. INFANRIX-IPV+Hib may be used for this booster dose if administration of the additional antigens at the same time is in accordance with official recommendations.



INFANRIX-IPV+Hib may be used as a booster dose for children who have previously been immunised with other vaccines that contain DTP, polio and Hib antigens.



Method of administration



INFANRIX-IPV+Hib is for deep intramuscular injection, in the anterolateral aspect of the thigh.



It is preferable that each subsequent dose is given into alternating limbs.



INFANRIX-IPV+Hib should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects. Firm pressure should be applied to the injection site (without rubbing) for at least two minutes.



INFANRIX-IPV+Hib should under no circumstances be administered intravascularly.



4.3 Contraindications



Hypersensitivity to the active substances or to any of the excipients or neomycin, polymyxin and polysorbate 80.



Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, polio or Hib vaccines.



INFANRIX-IPV+Hib is contra-indicated if the child has experienced an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine.



As with other vaccines, the administration of INFANRIX-IPV+Hib should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection, however, is not a contra-indication.



4.4 Special Warnings And Precautions For Use



As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.



If any of the following events have occurred in temporal relation to receipt of any DTP-containing vaccine, the decision to give subsequent doses of vaccine containing a pertussis component should be carefully considered.



• Temperature of



• Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination.



• Persistent, inconsolable crying lasting



• Convulsions with or without fever, occurring within 3 days of vaccination.



There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh possible risks, particularly since the events are not associated with permanent sequelae. According to available clinical data, the risk of such reactions is lower with acellular pertussis vaccines than with whole cell pertussis vaccines.



As for any vaccination, the risk-benefit of immunising with INFANRIX-IPV+Hib or deferring this vaccination should be weighed carefully in an infant or in a child suffering from a new onset or progression of a severe neurological disorder.



The Hib component of the vaccine does not protect against diseases due to other types of Haemophilus influenzae nor against meningitis caused by other organisms.



A history of febrile convulsions, a family history of convulsions, a family history of Sudden Infant Death Syndrome (SIDS) and a family history of an adverse event following DTP, IPV and/or Hib vaccination do not constitute contra-indications to administration of INFANRIX-IPV+Hib.



Human Immunodeficiency Virus (HIV) infection is not considered to be a contra-indication to administration of INFANRIX-IPV+Hib.



The expected immunological response may not be obtained after vaccination of immunosuppressed patients, e.g. patients on immunosuppressive therapy.



Excretion of capsular polysaccharide antigen in the urine has been described following receipt of Hib vaccines. Therefore false positive antigen detection test results are possible within 1-2 weeks of vaccination.



Administration of INFANRIX-IPV+Hib should be recorded in the patient's International Vaccination Certificate.



The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered when administering the primary immunisation series to very premature infants (born



As the benefit of the vaccination is high in this group of infants, vaccination should not be withheld or delayed.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



If INFANRIX-IPV+Hib is to be given at the same time as another injectable vaccine(s), the vaccines should always be administered at different injection sites.



As with other vaccines it may be expected that, in patients receiving immunosuppressive therapy or patients with immunodeficiency, an adequate response may not be achieved.



4.6 Pregnancy And Lactation



As INFANRIX-IPV+Hib is not intended for use in adults, information on the safety of the vaccine when used during pregnancy or lactation is not available.



4.7 Effects On Ability To Drive And Use Machines



Not applicable.



4.8 Undesirable Effects



- Clinical trials



The safety profile presented below is based on data from more than 3500 subjects.



As has been observed for DTPa and DTPa-containing combinations, an increase in local reactogenicity and fever was reported after booster vaccination with INFANRIX IPV+Hib with respect to the primary course.



Frequencies per dose are defined as follows:



Very common: (



Common: (



Uncommon: (



Rare: (



Very rare: (< 1/10,000)



Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.



Blood and lymphatic system disorders



Uncommon: lymphadenopathy



Nervous system disorders:



Very common: somnolence



Respiratory, thoracic and mediastinal disorders:



Uncommon: bronchitis, cough, rhinorrhoea



Gastrointestinal disorders:



Common: diarrhoea, vomiting



Skin and subcutaneous tissue disorders



Uncommon: urticaria, rash



Rare: pruritus, dermatitis



Metabolism and nutrition disorders



Very common: appetite lost



Infections and infestations



Uncommon: upper respiratory tract infection



General disorders and administration site conditions:



Very common: fever (



Common: injection site reactions including induration, local swelling at the injection site (>50 mm)1



Uncommon: diffuse swelling of the injected limb, sometimes involving the adjacent joint1, fever2>39.5°C, fatigue



Psychiatric disorders:



Very common: crying abnormal, irritability, restlessness



- Post-marketing surveillance



Nervous system disorders:



Collapse or shock-like state (hypotonic-hyporesponsiveness episode), convulsions (with or without fever).



Respiratory, thoracic and mediastinal disorders:



Apnoea3[see 4.4 for apnoea in very premature infants (



Skin and subcutaneous tissue disorders:



Angioneurotic oedema3



General disorders and administration site conditions:



Swelling of the entire injected limb1, injection site vesicles3



Immune system disorders



Allergic reactions (including anaphylactic3 and anaphylactoid reactions)



1Children primed with acellular pertussis vaccines are more likely to experience swelling reactions after booster administration in comparison with children primed with whole cell vaccines. These reactions resolve over an average of 4 days.



2common with booster vaccination



3reported with GSK's DTPa containing vaccines



4.9 Overdose



Not applicable.



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



Pharmaco-therapeutic group: Bacterial and viral vaccines combined, ATC code J07CA06



Results obtained in the clinical studies for each of the components are summarised in the tables below:



Percentage of subjects with antibody titres

















































































Antibody



(cut-off)




3-5 months



N= 86



(1 trial)



%




1.5-3.5-6 months



N= 62



( 1 trial)- %




2-3-4 months



N= 337



( 3 trials)



%




2-4-6 months



N= 624



(6 trials)



%




3-4-5 months



N= 127



(2 trials)



%




3-4.5-6 months



N=198



(1 trial)



%




Anti-diphtheria



(0.1 IU/ml)*




94.1




100




98.8




99.3




94.4




99.5




Anti-tetanus



(0.1 IU/ml)*




100.0**




100




99.7




99.8




99.2




100




Anti-PT



(5 EL.U/ml)




99.5**




100




99.4




100




98.4




100




Anti-FHA



(5 EL.U/ml)




99.7**




100




100




100




100




100




Anti-PRN



(5 EL.U/ml)




99.0**




100




100




100




100




100




Anti-Polio type 1



(1/8 dilution)*




93.0




ND




99.1




99.5




100




100




Anti-Polio type 2



(1/8 dilution)*




95.3




ND




95.7




99.0




99.2




100




Anti-Polio type 3



(1/8 dilution)*




98.8




ND




100




100




99.2




99.4




Anti-PRP (Hib)



(0.15 μg/ml)*




83.7




100




98.5




98.5




100




98.4




Anti-PRP (Hib)



(1.0 μg/ml)




51.2




87.1




68.5




76.0




97.6




81.2



* cut-off accepted as indicative of protection



** Post dose 2 results from studies where DTPa-HB-IPV/Hib was administered in a schedule 3, 5 and 11 Months of age.



Percentage of subjects with antibody titres





































Antibody



(cut-off)




Booster vaccination at 11/12 months of age following a 3-5 month primary course



N =184



(1 trial)



%




Booster vaccination during the second year of life following a three dose primary course



N = 1326 (9 trials)



%




Anti-diphtheria



(0.1 IU/ml)*




100




99.8




Anti-tetanus



(0.1 IU/ml)*




99.9**




99.9




Anti-PT



(5 EL.U/ml)




99.9**




99.7




Anti-FHA



(5 EL.U/ml)




99.9**




100




Anti-PRN



(5 EL.U/ml)




99.5**




99.9




Anti-Polio type 1



(1/8 dilution)*




99.4




99.9




Anti-Polio type 2



(1/8 dilution)*




100




100




Anti-Polio type 3



(1/8 dilution)*




99.4




100




Anti-PRP (Hib)



(0.15 μg/ml)*




100




100




Anti-PRP (Hib)



(1.0 μg/ml)




96.7




99.2



* cut-off accepted as indicative of protection



** Post dose 3 results from studies where DTPa-HB-IPV/Hib was administered in a schedule 3, 5 and 11 Months of age.



The effectiveness of the GlaxoSmithKline Biologicals' Hib component (when combined with DTPa, DTPa-IPV or DTPa-HBV-IPV) has been and continues to be investigated via an extensive post-marketing surveillance study conducted in Germany. Over a 4.5 year follow-up period, the effectiveness of DTPa/Hib or DTPa-IPV/Hib vaccines was 96.7% for a full primary series and 98.5% for a booster dose (irrespective of priming). Over a 3 year follow-up period, the effectiveness of hexavalent vaccines was 92.8% for a full primary series and 100% for a booster dose.



5.2 Pharmacokinetic Properties



Evaluation of pharmacokinetic properties is not required for vaccines.



5.3 Preclinical Safety Data



Preclinical data reveal no special hazard for humans based on conventional studies of safety, specific toxicity and compatibility of ingredients.



6. Pharmaceutical Particulars



6.1 List Of Excipients



Lyophilised HIB component:



Lactose



Liquid DTPa-IPV component:



Sodium chloride



2-phenoxyethanol



Medium 199 (as stabilizer containing amino acids, mineral salts, vitamins and other substances)



Water for injections



For adjuvants, see section 2.



6.2 Incompatibilities



In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.



6.3 Shelf Life



The shelf life of the vaccine components before reconstitution is 36 months.



After reconstitution, the vaccine should be injected immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should normally not be longer than 8 hours at +2°C to +8°C (in a refrigerator).



6.4 Special Precautions For Storage



Store in a refrigerator (2°C – 8°C)



Do not freeze.



Store in the original package, in order to protect from light.



6.5 Nature And Contents Of Container



Powder in vial (type I glass) with stopper (chlorobutyl).



0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger stopper (chlorobutyl) with or without needles. Pack size of 1, 10, 20, 25, 40, 50 and 100.



Not all pack sizes may be marketed.



6.6 Special Precautions For Disposal And Other Handling



Upon storage of the DTPa-IPV suspension, a white deposit and clear supernatant can be observed in the syringe. This is not a sign of deterioration.



The syringe should be well shaken to obtain a homogeneous suspension. The DTPa-IPV suspension in the syringe, the Hib powder in the vial and the reconstituted vaccine should be inspected visually for any foreign particulate matter and/or abnormal physical appearance prior to administration. In the event either is observed, the vaccine should be discarded.



The vaccine is reconstituted by adding the entire contents of the pre-filled syringe of DTPa-IPV suspension to the vial containing the Hib powder. The mixture should then be injected immediately. The full reconstitution instructions are:



1. Shake the pre-filled syringe containing the DTPa-IPV suspension



2. Attach a needle to the pre-filled syringe of DTPa-IPV and inject the contents of the syringe into the Hib vial.



3. With the needle still inserted, shake the Hib vial vigorously and examine for complete dissolution.



4. Withdraw the entire mixture back into the syringe.



5. Replace the needle with an appropriate size needle for injection and administer the vaccine.



6. If the vaccine is not administered immediately, shake the solution vigorously again before injection.



7. Any unused reconstituted vaccine should be discarded safely in accordance with local regulations.



7. Marketing Authorisation Holder



SmithKline Beecham plc



Trading as:



GlaxoSmithKline UK



Stockley Park West, Uxbridge



Middlesex, UB11 1BT



8. Marketing Authorisation Number(S)



PL10592/0216



9. Date Of First Authorisation/Renewal Of The Authorisation



25 January 2005



10. Date Of Revision Of The Text



4 February 2009



11. LEGAL CATEGORY


POM




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